Solubility enhancement of simvastatin and atorvastatin by arginine: Molecular dynamics and related solution chemistry using viscometric analysis

Abstract

The solubility enhancement of model statin based drugs such as simvastatin (SMV) and atorvastatin (ATV) has been achieved in the presence of arginine (ARG). Herein, the drug molecules (SMV, and ATV) are considered as solute, whereas ARG the cosolute. The present study aims to illustrate the solute-solvent interaction, solute-cosolute interaction and the thermodynamic parameters during the solubilization of the above drug candidates in water in the presence of ARG. Viscosity values of ARG, ARG-SMV, and ARG-ATV systems were determined in water containing different concentrations (0.01, 0.02, 0.04, 0.09, 0.18, 0.36 and 0.73) mol·dm−3 aqueous ARG, with saturated presence of SMV (SMV-ARG) and ATV (ATV-ARG) at four different temperatures (298.25, 303.15, 308.15, and 313.15K). Viscosity values were evaluated in terms of AF (Falken-Hagen coefficient), BJ (Jones-Dole coefficient), dB/dt, Δμ2° (contribution per mole of the solute to free), Δμ1° (corresponding value for pure solvent) and η₀Λ₀ (Walden product). Additionally, the viscometric data were explained on the basis of equations proposed by Einstein, Vand and Moulik.